According to the dictionary for clinical trials “concomitant medications are the drugs that are not being studied but which a patient is taking through all or part of a study. Pentazocine Low doses of the mixed agonist–antagonist pentazocine produce euphoria, sedation, impotence, and anhidrosis; higher doses cause headache, nausea, blurred vision, diplopia, tachycardia, hypertension, urinary retention, depressed respiration, dysphoria, delusions, hallucinations, and seizures.5 Subcutaneous or intramuscular injections of pentazocine cause severe focal skin and muscle fibrosis, the result of precipitation of the acidic drug.25. Minimisation of unwanted effects. clinical studies. Fortunately, new electronic technologies are now available to address this challenge. β-blockers inhibit the β-adrenergic glycogenolysis in liver and skeletal muscle and increase indirectly the insulin effect. The drugs that have been associated with increased theophylline clearance are relatively few; all are known to be inducers of cytochrome P-450 enzymes. This is one reason why combination overdoses can have such adverse medical consequences. Few studies have examined the impact of CM use on trial eligibility. Hence, there is a point where a thorough concomitant medication analysis is absolutely appropriate and may ultimately act as a supporting piece of evidence. Oxcarbazepine metabolism is unaffected by several inhibitors of carbamazepine metabolism. Beyond that, the earliest indication of a serious adverse event may have been self-treated with an OTC concomitant medication. A similar effect may be evident in chronically alcohol-dependent patients with coincidental hepatic cirrhosis and portocaval shunting. Package label. Sujay started as employee #6 and was instrumental in the growth of Model N to 600 employees, over $100M in revenue, and its eventual IPO (NYSE: MODN). Most reports of Phase 1 trials do not contain a description of the types of concomitant medications taken by the study participants in the trial, or any kind of analysis as to whether those medications might interact with the drug under study. When it is substituted for carbamazepine, plasma concentrations of concomitant drugs, such as valproate and neuroleptic drugs, can rise, owing to de-induction, leading to potential toxicity [57,58]. Until recently, effective tracking and analysis of con-meds in clinical trials was simply not on the radar for many pharma companies. Well -analyzed conmeds can indicate which adverse events and first -line medications are linked to the experimental … Lofepramine also has a short half-life but since this compound functions as a ‘pro-drug’ with rapid conversion to desipramine, the half-life figure is of less clinical importance. Fixed-dose drug combinations are appropriate for: Convenience, with improved patient compliance, is appropriate with two drugs used at constant dose, long term, for an asymptomatic condition, e.g. Medication-related exclusion criteria are among the most common barriers to enrollment in clinical trials. Overall, however, half-lives are compatible with once daily dosing and steady state within 5–7 days. The list of agents that decrease theophylline clearance is extensive (Box 65-2). Immunosuppressive agents and concomitant drugs such as diuretics and βblockers can have a negative effect on the lipid profile, while impaired renal function with or without proteinuria can also contribute.14–17 Known risk factors for raised total cholesterol and low-density lipoprotein (LDL) cholesterol following transplantation include obesity, male gender, and ethnicity.18,19, The lipoprotein profile following renal transplantation is characterized by an increase in both total cholesterol and LDL cholesterol levels.20–24 An increase of around 25% to 30% in total cholesterol is typical.20,25 The peak incidence of hypercholesterolemia occurs 3 to 6 months post-transplant and remains stable at an elevated level from 12 months after transplantation.26–28 It is estimated that 60% of the renal transplant population has a total cholesterol level above 240 mg/dL (6.2 mmol/L) and LDL cholesterol level above 132 mg/dL (3.4 mmol/L).29 Changes in high-density lipoprotein (HDL) cholesterol after transplantation are more variable, with studies reporting unchanged, increased, or decreased levels.17,30,31 These differences may be partly due to variations in the dose of corticosteroids used in each trial. One factor may come from taking concomitant treatments with an efficacy on the studied outcomes. Sujay was most recently Senior VP of Global Corporate Strategy and Development at Model N, where he filled multiple roles, from corporate development to overseeing their life sciences analytics and SaaS business unit. Increased dosage requirements of insulin may occur with adrenaline, chlorpromazine, corticosteroids, oral contraceptives, thiazide diuretics and thyroid hormones; there have also been isolated reports of increased insulin requirements or aggravation of hyperglycaemia with chlordiazepoxide, cyclophosphamide, dobutamine and isoniazid. The ciclosporin trough serum concentration and serum sodium concentration fell after oxcarbazepine was added. In patients with risks for NSAID toxicity, avoiding potent drugs with a long half-life or extended-release formulations is prudent. The concomitant chemotherapy was not identified in FDA’s review. We use cookies to help provide and enhance our service and tailor content and ads. https://www.pharmalive.com/wp-content/uploads/2016/08/Sujay_Jadhav.jpg, https://www.pharmalive.com/wp-content/uploads/2020/01/Pharmalive_4c-300x37.png, Concomitant medications in clinical trials: Why the stakes are high, © Copyright - PharmaLive and Outcomes LLC |, U.S. panel backs approval of Egalet’s abuse-resistant painkiller, Novo Nordisk cuts forecasts on tough U.S. market. Concomitant medications have always been a part of inclusion and exclusion criteria used to allow patients to take part in trials, but once an individual was admitted to a study, there was typically very little, if any, tracking by sponsors of the subtle impacts those medications might have on trial results. A further reason why tricyclic effects can be so toxic in overdose relates to changes that occur in kinetic variables (see below). In these cases, the initial con-med data quality is very high and then may drop off dramatically after randomization. Therapeutic aims should be clear. This is important for, not only reducing the overall cost of healthcare, but speeding the delivery and quality of life-saving therapies to patients. CONCOMITANT MEDICATIONS LOG. A number of drugs interfere with hepatic metabolism of tricyclics (see below), but of particular note is alcohol, which has a triphasic effect. Enzyme-inducing anticonvulsants cause a modest reduction in monohydroxycarbazepine concentrations [57]. The proliferation-signal inhibitors (PSI), everolimus and sirolimus, are stronger inducers of hyperlipidemia than CNI agents.52–54 The mechanisms by which PSIs affect lipid levels may be related to changes in lipoprotein lipase55 and an increased production of triglycerides with increased secretion of VLDL.56 Interference with an insulin-dependent signaling pathway has also been suggested as a means by which PSI therapy may disturb lipid metabolism.56 Regardless of the mechanisms involved, alterations in blood lipid levels appear to be related to the trough level of PSIs and decrease over time post-transplant as PSI blood concentrations are reduced.48,52,57 Lipid data from two large controlled studies in which renal transplant patients were converted to sirolimus have been analyzed by Blum.58 Sirolimus-treated patients had higher lipid levels than controls, but the difference diminished over time. Concomitant use of psychoactive medications is a common practice in most clinical trials of antidepressant medications. For example, con-meds are often collected by nursing staff, but after randomization, the con-med data is typically collected as part of the medical doctor’s consultation with the patient. Death considered by investigator to not be related to Cimzia … [m]alignancy is a recognized safety concern with treatment with TNF-α antagonists.77, MICHAEL W. SHANNON MD, MPH, in Haddad and Winchester's Clinical Management of Poisoning and Drug Overdose (Fourth Edition), 2007. 83% of study participants in a study of levetiracetam, an anticonvulsant agent, were taking at least 1 concomitant medication. It is therefore paramount that pharmacists and researchers alike are prepared to manage possible drug-drug interactions (DDIs) in patients who agree to participate in clinical trials. 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